A novel high-performance liquid chromatography with diode array detector method for the simultaneous quantification of the enzyme-reactivating oximes obidoxime, pralidoxime, and HI-6 in human plasma.

Autor: Kranawetvogl T; Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.; Walther-Straub-Institut, Ludwig-Maximilians-Universität, Munich, Germany., Steinritz D; Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.; Walther-Straub-Institut, Ludwig-Maximilians-Universität, Munich, Germany., Thiermann H; Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany., John H; Bundeswehr Institute of Pharmacology and Toxicology, Munich, Germany.
Jazyk: angličtina
Zdroj: Drug testing and analysis [Drug Test Anal] 2020 Jul; Vol. 12 (7), pp. 938-947. Date of Electronic Publication: 2020 Apr 23.
DOI: 10.1002/dta.2800
Abstrakt: Oximes such as pralidoxime (2-PAM), obidoxime (Obi), and HI-6 are the only currently available therapeutic agents to reactivate inhibited acetylcholinesterase (AChE) in case of intoxications with organophosphorus (OP) compounds. However, each oxime has characteristic agent-dependent reactivating efficacy, and therefore the combined administration of complementary oximes might be a promising approach to improve therapy. Accordingly, a new high-performance liquid chromatography method with diode-array detection (HPLC-DAD) was developed and validated allowing for simultaneous or single quantification of 2-PAM, Obi, and HI-6 in human plasma. Plasma was precipitated using 5% w/v aqueous zinc sulfate solution and subsequently acetonitrile yielding high recoveries of 94.2%-101.0%. An Atlantis T3 column (150 × 2.1mm I.D., 3 μm) was used for chromatographic separation with a total run time of 15 min. Quantification was possible without interferences within a linear range from 0.12 to 120 μg/mL for all oximes. Excellent intra-day (accuracy 91.7%-98.6%, precision 0.5%-4.4%) and inter-day characteristics (accuracy 89.4%-97.4%, precision 0.4%-2.2%) as well as good ruggedness were found. Oximes in processed samples were stable for at least 12 h in the autosampler at 15°C as well as in human plasma for at least four freeze-thaw cycles. Finally, the method was applied to plasma samples of a clinical case of pesticide poisoning.
(© 2020 John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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